The importance of in-silico studies in drug discovery

The use of in-silico research in drug development is growing. Aspects of drug discovery and development, such as virtual ligand screening and profiling, target and lead finding, and compound library creation, are simulated by computational approaches. Databases, pharmacophores, homology models, quantitative structure–activity connections, machine learning, data mining, network analysis tools, and computer-based data analysis tools are examples of in-silico techniques. These techniques are mostly applied in conjunction with the production of in vitro data to build models that facilitate the identification and refinement of new compounds by providing insight into their features related to absorption, distribution, metabolism, and excretion

Computational studies demonstrating dithymoquinone of Nigella sativa as a potential anti-dengue agent: Short review

Dengue is acute tropical infectious illness, which is spread by mosquitoes, has presented a significant threat to public health worldwide. Unfortunately, there are no drugs that have been clinically proven to be effective at treating or preventing dengue. The development of some drugs is significantly hampered by our incomplete understanding of dengue pathogenesis. This short review provides a brief description of potential action against DENV of dithymoquinone to develop an anti-DENV inhibitor. In-vitro, in-vivo and clinical trials are required to establish the effectiveness and safety of dithymoquinone as an anti-dengue therapy, even though computational studies have demonstrated antiviral activity against DENV

Anti-diabetic activity of phloretin against maltase-glucoamylase using docking, pharmacokinetics and pharmacophore studies

A metabolic condition known as diabetes mellitus is characterized by hyperglycemia brought on by either inadequate insulin production, resistance to insulin action, or both. The anti-diabetic medications that are now on the market either impact how much glucose is absorbed and excreted or how much insulin is secreted without affecting insulin resistance. This study used in-silico methods to assess the efficacy of phloretin as anti-diabetic drug against maltase-glucoamylase. Phloretin displayed strong binding to the maltase-glucoamylase protein with good docking scores (-7.4 kcal/mol), as opposed to co-crystallized ligand (-6.2 kcal/mol). In terms of physicochemical qualities, drug-likeness, and medicinal chemistry properties, Phloretin also performed best. The results of molecular docking and data acquired from pharmacokinetic characteristics of phloretin may be used further for the creation of newer maltase-glucoamylases with potential anti-diabetic properties and improved pharmacokinetic profiles

Cancer drug resistance is a serious threat in Bangladesh

Cancer drug resistance is a serious issue in Bangladesh that must be addressed with effective solutions. The growth of resistant bacterial strains, inappropriate use of antimicrobials, and inadequate healthcare standards in Bangladesh have resulted in a severe problem with cancer medication resistance. A comprehensive strategy will be needed to address these problems, one that includes expanding knowledge of antibiotic resistance, bettering healthcare system regulation, and developing more potent cancer therapies

Virtual screening of pyrazole derivatives of usnic acid as new class of anti-hyperglycemic agents against PPARγ agonists

The finest sources of therapeutic agents are natural products, and usnic acid is a secondary metabolite derived from lichen that has a wide range of biological actions, including anti-viral, anti-cancer, anti-bacterial, and anti-diabetic (hyperglycemia). Based on the hyperglycemia activity of UA, this work seeks to identify new anti-hyperglycemia medicines by virtual screening of pyrazole derivatives of UA. Seven hit compounds (Compounds 1, 5, 6, 7, 17, 18 and 33), which finally go through docking-based screening to produce the lead molecule, were identified by the physicochemical attributes, drug-likeliness, and ADMET prediction. The docking score for the chosen compounds containing PPARγ agonists ranged from -7.6 to -9.2 kcal/mol, whereas the docking goal for compounds 5, 6, and 7 was -9.2 kcal/mol. Based on the binding energy and bound amino acid residues as well as compared to the reference compound, compound-6 considered as lead compound. Furthermore, the MD simulation of 3CS8-Compound-6 and 3CS8-Rosiglitazone complexes were performed to verify the stability of these complexes and the binding posture acquired in docking experiments. The compound-6 had strong pharmacological characteristics, bound to the PPARγ agonist active site, and was expected to reduce the activity of the receptor, according to the virtual screening results. It must be justified to conduct both in-vitro and in-vivo experiments to examine the efficacy of this compound

In silico analysis for discovery of dengue virus inhibitor from natural compounds

Dengue fever is a growing global health problem, with millions of virus illnesses occurring each year. Unfortunately, there is no approved treatment available. DENV NS5 RdRp protease produced by the dengue virus (DENV) is being investigated as a promising therapeutic target for developing efficient dengue treatments. Dengue virus propagation is aided by RdRp protease. This work used in-silico ligand-based and structure-based techniques to generate a DENV-2 NS5 RdRp protease inhibitor. Firstly, a ligand-based Lipinski's rule of five and an ADMET prediction was utilized to screen 42 putative antiviral natural compounds. The tested compounds were docked into the active region of DENV-2 NS5 RdRp protease. A lead compound (3'-O-Methyldiplacol) is recommended as a promising inhibitor of NS5 RdRp protease based on docking scores. This work discovered a possible DENV-2 NS5 RdRp protease inhibitor applying in-silico screening that might be beneficial in treating Dengue. Studying the effectiveness of this compound through in vitro and in vivo experimentations must be warranted

Insights on the synthesis of asymmetric curcumin derivatives and their biological activities

Curcumin is a small organic molecule with pleiotropic biological activities. However, its multiple structural-pharmacokinetic challenges prevent its development into a clinical drug. Various structural modifications have been made to improve its drug profile. In this review, we focus on the methods adopted in the synthesis of asymmetric curcumin derivatives and their biological activities and forecast the future of this exciting class of compounds in the field of medicine

Inhibitory effect of Sinapic acid derivatives targeting structural and non-structural proteins of dengue virus serotype 2 An in-silico assessment

DENV infects 50–100 million individuals, and 500,000 of them go on to acquire the more serious dengue hemorrhagic fever, which causes around 20,000 fatalities every year. Despite its widespread nature, there is no medication licenced to treat this condition. The purpose of this work is to identify anti-DENV medicines from sinapic acid (SA) derivatives utilising in-silico evaluation through docking and pharmacokinetics investigations. For the DENV-2 envelop protein, 1-O-β-d-glucopyranosyl sinapate had a significant docking score of −7.7 kcal/mol, while sinapoyl malate had a docking score of −6.7 kcal/mol for the DENV-2 NS2B/NS3 protein. Additionally, according to the PASS server, 1-O-β-d-glucopyranosyl sinapate and sinapoyl malate have a wide range of enzymatic activities since their probability active (Pa) values is > 0.700. These compounds exhibit a numerous pharmacological effect through activating the body's enzymes, according to analyses of their pharmacokinetic qualities. Accordingly, these substances showed acute toxicity rates at LD50 log10 (mmol/g) and LD50 (mg/g) concentrations when administered via various routes, including intraperitoneal, intravenous, oral, and subcutaneous. The result of this research suggests, 1-O-β-d-glucopyranosyl sinapate and sinapoyl malate may function as possible inhibitors to halt the DENV, and more in-vitro and in-vivo research is required to validate their activity and other features

Concerns regarding SARS-CoV-2 JN.1 mutations should be raised

JN.1 is a new variant of SARS-CoV-2 which is a subvariant of Omicron (BA.2.86) was first discovered in the USA in September 2023. The virus’s capacity to spread and elude the immune system may be impacted by a single alteration in the spike protein, which serves as its distinguishing feature. JN.1 has been classified as an interesting variety by the World Health Organisation. JN.1 might lead to a rise in infections, or its possible influence on public health is yet premature. Current immunisations, examinations, and therapies are still anticipated to combat JN.1

In-silico Studies of Usnic Acid against DENV-3 Methyltransferase

There is currently no antiviral medication for dengue, a highly fatal tropical infectious disease spread by the Aedes aegypti and Aedes albopictus mosquitoes. The most conserved of the four Dengue serotypes and an essential element in viral replication, Dengue NS5 MTase is a promising therapeutic target. Applying in-silico techniques such as molecular docking, pharmacokinetics, and pharmacophore analysis, we intend to discover novel inhibitors against Dengue NS5 MTase from Usnic acid. In the end, the docking results indicated that usnic acid had satisfactory docking values of -9.3 kcal/mol. We were able to confirm that the usnic acid had higher potential scores in docking and bound amino acids than the reference compound during our in-silico evaluation. Molecular docking, pharmacokinetics, and pharmacophore evaluations revealed that usnic acid has high pharmacological potential. Additionally, we anticipate that the testing in vitro and in vivo of usnic acid would indicate potential medicinal benefits